The initiation of antigen specific immune responses by macrophages requires cellular expression of Ia antigens. The in vitro regulation of macrophage Ia antigen expression was studied. We have found that a soluble mediator biochemically similar to immune interferon (IFN-gamma) induces Ia antigen deficient (Ia-) macrophages to express Ia antigens. Current research has focused on conditions that favor the Ia state, which may be important in the immunosuppresed state. Bacterial endotoxin (LPS) inhibited IFN-gamma induction of macrophage Ia antigen expression. This inhibitory effect was abrogated by indomethacin, a prostaglandin synthetase inhibitor, and mimicked bhy exogenous prostaglandin E2 and dibutyryl cAMP. The in vivo relevance of these in vitro regulatory pathways is being determined by correlation of macrophage Ia antigen expression and serum IFN-gamma and PGE2 levels. Finally the in vitro regulation of human monocyte Ia-like (DR) antigen expression has been studied. Peripheral blood monocytes, neonatal cord blood monocytes and HL60 cell line promonocytes expressed DR antigens in response to recombinant IFN-alpha